Lorenzo Menicanti

Coronary Bypass Surgery with or without Surgical Ventricular Reconstruction

BACKGROUND Surgical ventricular reconstruction is a specific procedure designed to reduce left ventricular volume in patients with heart failure caused by coronary artery disease. We conducted a trial to address the question of whether surgical ventricular reconstruction added to coronary-artery bypass grafting (CABG) would decrease the rate of death or hospitalization for cardiac causes, as compared with CABG alone. METHODS Between September 2002 and January 2006, a total of 1000 patients with an ejection fraction of 35% or less, coronary artery disease that was amenable to CABG, and dominant anterior left ventricular dysfunction that was amenable to surgical ventricular reconstruction were randomly assigned to undergo either CABG alone (499 patients) or CABG with surgical ventricular reconstruction (501 patients). The primary outcome was a composite of death from any cause and hospitalization for cardiac causes. The median follow-up was 48 months. RESULTS Surgical ventricular reconstruction reduced the end-systolic volume index by 19%, as compared with a reduction of 6% with CABG alone. Cardiac symptoms and exercise tolerance improved from baseline to a similar degree in the two study groups. However, no significant difference was observed in the primary outcome, which occurred in 292 patients (59%) who were assigned to undergo CABG alone and in 289 patients (58%) who were assigned to undergo CABG with surgical ventricular reconstruction (hazard ratio for the combined approach, 0.99; 95% confidence interval, 0.84 to 1.17; P=0.90). CONCLUSIONS Adding surgical ventricular reconstruction to CABG reduced the left ventricular volume, as compared with CABG alone. However, this anatomical change was not associated with a greater improvement in symptoms or exercise tolerance or with a reduction in the rate of death or hospitalization for cardiac causes. (ClinicalTrials.gov number, NCT00023595.)

Risk of assessing mortality risk in elective cardiac operations: age, creatinine, ejection fraction, and the law of parsimony.

Background— Several mortality risk scores exist in cardiac surgery. All include a considerable number of independent risk factors. In elective cardiac surgery patients, the operative mortality is low, the number of events recorded per year is limited, and the risk model may be overfitted. The present study aims to develop and validate an operative mortality risk score for elective patients based on a limited number of factors. Methods and Results— The development series included 4557 adult patients who had undergone an elective cardiac operation at our institution from 2001 to 2003; the validation series includes the 4091 patients who subsequently underwent an operation. Three independent factors were included in the mortality risk model: age, creatinine, and left ventricular ejection fraction (ACEF). The ACEF score was computed as follows: age (years)/ejection fraction (%)+1 (if serum creatinine value was >2 mg/dL). The ACEF score was compared with 5 other risk scores in the validation series. Discriminatory power (accuracy) was defined with a receiver-operating characteristics analysis. The best accuracy was achieved by the Cleveland Clinic score (0.812), with ACEF score just below it (0.808). In coronary operations, the 2 scores performed equally well (0.815 versus 0.813), and in isolated coronary operations, the best accuracy was achieved by ACEF (0.826), with the Cleveland Clinic score at 0.806. Conclusion— A risk model limited to 3 independent predictors has similar or better accuracy and calibration compared with more complex risk scores if applied to elective cardiac operations.

Influence of mitral regurgitation repair on survival in the surgical treatment for ischemic heart failure trial.

Background— Whether mitral valve repair during coronary artery bypass grafting (CABG) improves survival in patients with ischemic mitral regurgitation (MR) remains unknown. Methods and Results— Patients with ejection fraction ⩽35% and coronary artery disease amenable to CABG were randomized at 99 sites worldwide to medical therapy with or without CABG. The decision to treat the mitral valve during CABG was left to the surgeon. The primary end point was mortality. Of 1212 randomized patients, 435 (36%) had none/trace MR, 554 (46%) had mild MR, 181 (15%) had moderate MR, and 39 (3%) had severe MR. In the medical arm, 70 deaths (32%) occurred in patients with none/trace MR, 114 (44%) in those with mild MR, and 58 (50%) in those with moderate to severe MR. In patients with moderate to severe MR, there were 29 deaths (53%) among 55 patients randomized to CABG who did not receive mitral surgery (hazard ratio versus medical therapy, 1.20; 95% confidence interval, 0.77–1.87) and 21 deaths (43%) among 49 patients who received mitral surgery (hazard ratio versus medical therapy, 0.62; 95% confidence interval, 0.35–1.08). After adjustment for baseline prognostic variables, the hazard ratio for CABG with mitral surgery versus CABG alone was 0.41 (95% confidence interval, 0.22–0.77; P=0.006). Conclusion— Although these observational data suggest that adding mitral valve repair to CABG in patients with left ventricular dysfunction and moderate to severe MR may improve survival compared with CABG alone or medical therapy alone, a prospective randomized trial is necessary to confirm the validity of these observations. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00023595.

Role of age in acute type A aortic dissection outcome: report from the International Registry of Acute Aortic Dissection (IRAD).

OBJECTIVE The increasing life expectancy of the population will likely be accompanied by a rise in the incidence of acute type A aortic dissection. However, because of an increased risk of cardiac surgery in an elderly population, it is important to define when, if at all, the risks of aortic repair outweigh the risk of death from unoperated type A aortic dissection. METHODS We analyzed 936 patients with type A aortic dissection enrolled in the International Registry of Acute Aortic Dissection from 1996 to 2004. Patients with type A aortic dissection were categorized according to patient age by decade and by surgical versus medical management, and outcomes of both management types were investigated in the different age groups. RESULTS The rate of surgical aortic repair decreased progressively with age, whereas surgical mortality significantly increased with age. Age 70 years or more was an independent predictor for mortality (38.2% vs 26.0%; P < .0001, odds ratio 1.73). The in-hospital mortality rate was significantly lower after surgical management compared with medical management until the age of 80 years. For patients aged 80 to 90 years, the in-hospital mortality appeared to be lower after surgical management (37.9% vs 55.2%; P = .188); however, this failed to reach clinical significance owing to the limited patient number in this age group. CONCLUSIONS Although the surgical mortality significantly increased with increased age, surgical management was still associated with significantly lower in-hospital mortality rates compared with medical management until the age of 80 years. Surgery may decrease the in-hospital mortality rate for octogenarians with type A aortic dissection and might be considered in all patients with type A aortic dissection regardless of age.

MicroRNA Dysregulation in Diabetic Ischemic Heart Failure Patients

Increased morbidity and mortality associated with ischemic heart failure (HF) in type 2 diabetic patients requires a deeper understanding of the underpinning pathogenetic mechanisms. Given the implication of microRNAs (miRNAs) in HF, we investigated their regulation and potential role. miRNA expression profiles were measured in left ventricle biopsies from 10 diabetic HF (D-HF) and 19 nondiabetic HF (ND-HF) patients affected by non–end stage dilated ischemic cardiomyopathy. The HF groups were compared with each other and with 16 matched nondiabetic, non-HF control subjects. A total of 17 miRNAs were modulated in D-HF and/or ND-HF patients when compared with control subjects. miR-216a, strongly increased in both D-HF and ND-HF patients, negatively correlated with left ventricular ejection fraction. Six miRNAs were differently expressed when comparing D-HF and ND-HF patients: miR-34b, miR-34c, miR-199b, miR-210, miR-650, and miR-223. Bioinformatic analysis of their modulated targets showed the enrichment of cardiac dysfunctions and HF categories. Moreover, the hypoxia-inducible factor pathway was activated in the noninfarcted, vital myocardium of D-HF compared with ND-HF patients, indicating a dysregulation of the hypoxia response mechanisms. Accordingly, miR-199a, miR-199b, and miR-210 were modulated by hypoxia and high glucose in cardiomyocytes and endothelial cells cultured in vitro. In conclusion, these findings show a dysregulation of miRNAs in HF, shedding light on the specific disease mechanisms differentiating diabetic patients.

Risk factors for renal dysfunction after coronary surgery: the role of cardiopulmonary bypass technique:

We studied 316 patients undergoing cardiopulmonary bypass for coronary artery surgery in order to determine perioperative risk factors for postoperative renal dysfunction A preliminary univariate analysis was performed by χ2 analysis for categorical data and Mann-Whitney U-test for continuous variables to detect significant correlations between each risk factor and the occurrence of moderate or severe renal dysfunction. Subsequently, a multiple logistic regression was applied to the three risk factors identified as predictive for severe renal dysfunction. Low cardiac output syndrome and need for banked blood transfusions combined with a low haematocrit value during cardiopulmonary bypass increase the probability of severe renal dysfunction in the postoperative course.

Postoperative antithrombin levels and outcome in cardiac operations

Objective:During cardiac operations with cardiopulmonary bypass surgery, antithrombin is consumed and low levels of antithrombin activity are commonly observed at admission to the intensive care unit (ICU). This study investigates the association between antithrombin activity at admission to the ICU (ICU-antithrombin activity) and various outcome variables. Design:The authors conducted a prospective, observational cohort study. Setting:The study was conducted at a university hospital. Patients:The study consisted of 647 consecutive patients who had undergone cardiac surgery with cardiopulmonary bypass. Measurements and Main Results:ICU-antithrombin activity significantly (p < .001) decreased with respect to preoperative values. As seen with univariate analysis, low levels of ICU-antithrombin activity were significantly associated with higher blood loss, prolonged mechanical ventilation time and ICU stay, a higher incidence of allogeneic blood products use, surgical reexploration, low cardiac output syndrome, adverse neurologic events, thromboembolic events, renal dysfunction, and hospital mortality. When corrected for the other explanatory variables, low levels of ICU-antithrombin activity remained independently associated with a prolonged ICU stay (p = .003) and with a higher incidence of surgical reexploration (p = .023), adverse neurologic events (p = .001), and thromboembolic events (p = .036). An ICU-antithrombin activity value of <58% was found to be predictive of prolonged ICU stay, with a sensitivity of 67% and a specificity of 83%. Conclusions:Low levels of ICU-antithrombin activity are associated with a poor outcome in cardiac surgery; ICU-antithrombin activity is predictive of prolonged ICU stay.

Predictors for heparin resistance in patients undergoing coronary artery bypass grafting

Heparin resistance (HR) is a common event in cardiac operations. At present, no clear recognition of the risk factors for HR has been reached. The aim of this study was to determine a predictive model for HR, based on the preoperative patient’s profile. Two hundred consecutive patients scheduled for elective coronary artery bypass operations were enrolled in a prospective trial. Demographics, type of preoperative anticoagulation therapy and preoperative coagulation profile were collected and statistically analysed with respect to the evidence of a HR. Heparin resistance was defined as at least one activated clotting time < 400 s after heparinization and/or the need for purified antithrombin III (AT-III) administration. With a multivariate analysis we could identify five predictors for HR: AT-III ≤ 60%; preoperative subcutaneous heparin therapy; intravenous heparin therapy; platelet count ≥ 300 000 cells/mm3; age ≥ 65 years. We conclude that HR is a predictable event. In the presence of all the risk factors, the likelihood of HR is 99%; in the absence of all of them, it is 10%. Predicting HR allows us to apply many possible therapeutic strategies.

Randomized, Double‐Blinded, Placebo‐Controlled Trial of Fibrinogen Concentrate Supplementation After Complex Cardiac Surgery

Background Postoperative bleeding after heart operations is still a common finding, leading to allogeneic blood products transfusion. Fibrinogen and coagulation factors deficiency are possible determinants of bleeding. The experimental hypothesis of this study is that a first-line fibrinogen supplementation avoids the need for fresh frozen plasma (FFP) and reduces the need for any kind of transfusions. Methods and Results This was a single-center, prospective, randomized, placebo-controlled, double-blinded study. One-hundred sixteen patients undergoing heart surgery with an expected cardiopulmonary bypass duration >90 minutes were admitted to the study. Patients in the treatment arm received fibrinogen concentrate after protamine administration; patients in the control arm received saline solution. In case of ongoing bleeding, patients in the treatment arm could receive prothrombin complex concentrates (PCCs) and those in the control arm saline solution. The primary endpoint was avoidance of any allogeneic blood product. Patients in the treatment arm had a significantly lower rate of any allogeneic blood products transfusion (odds ratio, 0.40; 95% confidence interval, 0.19 to 0.84, P=0.015). The total amount of packed red cells and FFP units transfused was significantly lower in the treatment arm. Postoperative bleeding was significantly (P=0.042) less in the treatment arm (median, 300 mL; interquartile range, 200 to 400 mL) than in the control arm (median, 355 mL; interquartile range, 250 to 600 mL). Conclusions Fibrinogen concentrate limits postoperative bleeding after complex heart surgery, leading to a significant reduction in allogeneic blood products transfusions. No safety issues were raised. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01471730.

Beneficial effects of duraflo II heparin-coated circuits on postperfusion lung dysfunction

BACKGROUND Heparin coating of the cardiopulmonary bypass circuit reduces the activation of the terminal part of the complement cascade. Conflicting data are reported concerning neutrophil activation and postoperative lung dysfunction. In this study, we compared three different types of oxygenator: a bubble oxygenator, a conventional hollow-fiber oxygenator, and a heparin-coated oxygenator and circuit. METHODS Sixty patients undergoing myocardial revascularization were randomly assigned to one of three oxygenator groups. All the patients were free from preoperative lung dysfunction. Lung function was studied with repeated measurements of respiratory index, intrapulmonary shunt, alveolar dead space, ventilation/perfusion ratio, and static thoracopulmonary compliance. RESULTS Immediately after cardiopulmonary bypass, the intrapulmonary shunt and respiratory index values in the bubble oxygenator and hollow-fiber oxygenator groups increased more than those in the heparin-coated oxygenator group. In the intensive care unit, the between-group difference in intrapulmonary shunt disappeared, but the within-group difference in respiratory index (from baseline) remained for the bubble oxygenator group. The other three variables did not significantly differ between groups. Intubation time and stay in the intensive care unit did not differ between groups. CONCLUSIONS Heparin-coated circuits exert a protective effect on pulmonary function. However, their use did not modify the postoperative clinical course of patients with normal lung function preoperatively.